Chapter 20: The Kidney Flashcards
What is the most common and 2nd most common causes of Chronic Renal Failure (CRF) and End-Stage Renal Disease (ESRD)?
- Diabetes = MOST common
- High BP = second most common
What is the single most important question to ask a patient suspected of having renal disease?
Why?
- - “Have you had this before?”
- Hx of disease can imply a significantly worse prognosis or chronicity
What is the average size of the kidney?
- 120-150 grams and continues to grow until late teens/early 20s
- Length: 10-12 cm
- Width: 6cm
How is the hilar area of the kidney different from the parenchyma?
Hilar, ureter and urinary bladder are lined by transitional cell epithelium
Why is the right kidney lower than the left?
Liver pushes it down
Where is the kidney located?
Renal angle: between the lower border of the 12th rib and lateral border of the erector spinae muscle.
If a patient comes in with kidney pain, what is its distribution?
Starts from renal angle and radiates forward (anterior) towards the groin.
How are the kidneys attached?
- Fascial plane, renal artery and vein, ureter and mesentary.
- There are NO suspensory ligments.
But what about the splenorenal ligament, is that a suspensory ligament that holds the kidney in place?
No
Do all small tumors form a mass?
NOOOO.
What is creatinine and in kidney dysfunctions, it is ↑ or ↓ ?
What about BUN levels?
-
Creatnine is a breakdown product of muscle metabolism. Usually, it is excreted NL.
- If kidney dysfunction:
- ↑ serum creatinine and BUN (blood urea nitrogen)
-
↓ urine creatinine and BUN
*
- If kidney dysfunction:
When is a renal biopsy performed?
Because of the invasivness, there must be DEFINITE indications of a kidney dysfunction.
What is always performed with a renal biopsy?
UA
Kidney diseases often result in edema.
What causes generalized edema vs localized edema?
- Generalized edema: Heart, kidney and liver failure
- Localized: only lung failure
Renal diseases can be catagorized based on what 4 compartments of the kidneys?
- Glomeruli (often immunologically mediated)
- Tubules (often toxic/infectious inury)
- Interstitium
- Blood vessels
In the kidneys,
- DM is mainly a __________ disease.
- Systemic HTN is mainly a _________ disease.
- DM= glomerular disease
- HTN= tubulointestinal disease (d/t vascular damage)
Glomerular disorders are though to be due to what?
Immunologic diseases (primary or secondary)
What is responsible for the long-term complications in diabetics?
Persistant hyperglycemia (glucotoxicity)
Azotemia
↑ BUN & ↑ creatinine d/t a ↓ in GFR
Pre-renal Azotemia
Azotremia d/t hypoperfusion of the kindeys (d/thypotension, shock, CHF, or cirrhosis of liver) W/O damage of the parenchyma
Post-renal azotemia
Azotremia d/t urine outflow is obstructed after leaving the kidney (distal to calyces and renal pelvis). If the obstruction is removed, azotemia is corrected.
Uremia
Azotremia + other clinical findings and signs like: metabolic, hematologic, endo, GI, neuro and CV effects
If Puttoff says uremia, what is the condition of the patient?
They are in chronic kidney diasease (CKD, same as chronic renal failure)
How does a patient with uremia progress and present?
How do we dx in children?
- Pt has nonspecific sx, which become chronic and worse overtime as the disease worsens.
- Dx in children is hard because of the non-specific sx.
Azotremia is often seen in _________ syndromes
Nephritic syndromes
Know the difference between nephrotic and nephritic syndromes
What is the NL GFR?
90-120 mL/min/1.73m2
Older ppl will lower GFR bc it varies w age.
What is acute kidney injury (AKI)/acute renal failure?
Severe cases show?
Reversible?
-
Rapid decline of GFR due to glomerular, interstitial, vascular or acute tubular injury (ATN).
- Severe cases will show: oliguria or anuria
- Reversible, or can progress to CKD.
Injury to what morphological structure of the kidney is the most common cause of Acute Kidney Injury?
Acute tubular injury (ATN)
What is Chronic Kidney Disease (CKD/Chronic Renal Failure)?
Mild/severe cases show?
Reversible?
Azotremia -> uremia
-
Persistantly ↓ GFR that is less than 60 mL/min/1.73 m2 for at least 3 months and/or persistent albuminuria.
-
Mild cases = clinically silent
- Severe cases= uremia
- Generally, irreversible
-
Mild cases = clinically silent
CKD affects _____ of all adults in the US.
11%
What is end-stage renal disease?
Less than 5% of NL GFR and the end stage of uremia.
What is rapidly progressive glomerulonephritis (RPGN)?
Nephritic syndrome with rapid decline (days-weeks) in GFR, indicating severe glomerular injury.
- Can manifest as: acute nephritis, proteinemia and acute renal failure
Glomerular disease is often associated with what 4 main systemic disorders?
1. SLE
2. Diabetes
3. Amyloidosis
4. Vasculitis
What clinical renal diseases are characterstic of tubulointestinal diseases?
- 1. UTI
- 2. Urinary tract obstruction
- 3. Renal tumors
Renal tubular defects and acute renal failure can be both glomerular and tubulointestinal.
What clinical renal diseases are characteristic of glomerular diseases?
1. Nephrotic/nephritic syndromes
2. Asymptomatic hematuria/proteinuria
3. CRF
Renal tubular defects and acute renal failure can be both glomerular and tubulointestinal.
Renal tubular defects and acute renal failure can be both glomerular and tubulointestinal.
What are isolated urinary abnormalities?
Glomerular hematuria and or subnephrotic proteinuria
What is the renal corpsucle?
Glomerulus and Bowmans capsule (urinary space), which captures the glomerular filtrate and sends it into the tubular system.
Which cells of the glomerulus are contractile, phagocytic, capable of proliferation, and laying down both matrix and collagen?
Mesangial cells
What is a diffuse vs. focal glomeruopathy?
- Diffuse = affects ALL of the glomeruli in kidney (more than 50%)
- Focal = not all glomeruli are affected; others are NL (less than 50%)
What is segmental vs. global glomerulopathy?
- Segmental: only PORTIONS of affected glomeruli are damaged
- Global: the entire glomerulus is affected.
Once any renal disease destroys nephrons and ↓ GFR to 30-50% of the normal rate, what happens?
Progression to ESRF occurs at a steady rate. The 2 major histological fxs are
- 1. FSGS (focal segmental glomerulosclerosis)
- 2. Tubulointerstitial fibrosis
What can cause progressive glomerular injury?
Primary or secondary glomerular injury
Progressive injury is due to a cycle of glomerular and nephron loss, followed by what?
Compensatory changes that will further cause injury and glomerulosclerosis and eventually, end-stage renal disease.
What is the principal glomerular manifestation of progressive glomerular injury?
Focal segmental glomerulosclerosis, eventually leading to global glomerular involvement and glomerular obsolencence.
The extent of damage to ___________ is MOST correlated to worsening renal function?
Tubulointerstitial damage,
rather than the severity of glomerular injury
What is the pathological response of the glomerulus to injury?
What do we see in acute vs chronic injury?
- Hypercellularity of
- -Endothelial and mesengial cells
- -Inflammatory cells (leukocytes)
- -Proliferation of epithelial cells & inflammatory cells => plasma proteins leaks into space => + coagulation factors => form crescents
- BM thickening and deposits
- Hyalinosis (injury of endothelium) and sclerosis (deposition of ECM)
- Acute: hypercellularity and crescents
- Chronic: BM thickening, hyalonisis and sclerosis
What can be used to visualize thickening of the capillary wall?
Light microscopy with PAS staining
What does electron microscopy show for basement membrane thickening?
Subendothelial/subepithelial deposits of immune complexes, fibrin, amyloid and increased synthesis of BM components.
What morphological change to the glomerulus is characterized by the accumulation of homogenous/eosinophilic material under light microscopy and is typically the end result of many forms of glomerular injury?
Hyalinosis
Chronic glomerular responses to injury include what 3 morphological changes?
- - Basement membrane thickening
- - Hyalinosis
- - Sclerosis
Glomerular injury is mostly d/t immune mechanisms.
How can Ab cause injury?
-
Ab react in glomerulus & ****
* bind to fixed intrinsic antigens => immune complex
* bind to planted antigens => immune complex- Can be exogenous (drugs, infections)
- Endogenous (DNA, immunoglobulins, immune complexes)
-
Ab react in glomerulus & ****
- Circulating Ab-Ag complex in glomerulus
* Endogenous
* Exogenous
- Circulating Ab-Ag complex in glomerulus
The major cause of glomerulonephritis is what?
In situ immune complex formation
What diseases are caused by in-situ formation of immune complexes?
- Anti-GBM nephrititis
- Membranous glomerulonephropathy
- Post-strep glomerulonephritis
….
In the Heymann model of glomerulonephritis (experimental counterpart oto membranous nephropathy), Abs reacts to what Ag?
This Ag is normally found where?
Megalin, normally found in epithelial cell (podocyte) foot processes
Which Ag underlies most cases of primary human membranous nephropathy?
M-type phospholipase A2 receptor (PLA2R)
In membranous nephropathy, Ab binding to PLA2R in glomerular epithelial cell membranes => leads compliment activation => immune complex forms where on the BM?
Characteristic BM appearance on light microscopy?
- SUBepithelial part of BM
- THICKENED BM appearance on light microscopy
what is the pattern of immune deposition seen in membranous nephropathy (in-situ immune complex deposition) with immunofluorescence,?
Reflects what?
- GRANULAR pattern
- d/t VERY localized antigen-AB interaction.
What is the antigen associated with anti-GBM nephritis?
NC1 domain of type 4 collagen Ag
What characteristic pattern seen with immunofluorescence in diseases caused by Abs directed against NL glomerular BM components (i.e., anti-GBM)?
Diffuse linear pattern bc Abs bind to intrinsic Ags along the entire legnth of GBM
Often anti-GBM Abs cross react with other BM’s, especially where?
What syndrome does this occur in?
- Lung alveoli, forming lesions in lung and kidney
- Goodpasture syndrome
What kind of glomerular damage occurs due to anti-GBM Abs?
Leading to which clinical syndrome?
- Causes severe necrotizing** and **crescentic glomerular damage
- Leading to rapidly progressive glomerulonephritis (RPGN)
EXOGENOUS Ags from which bacteria/viruses create circulating immune complexes leading to glomerulonephritis?
What are endogenous sources?
- - Streptococcal proteins
- - Surface Ag of HBV and viral antigens of HCV
- - Ags of T_reponema pallidum_ and P_lasmodium falciparum_
Endogenous: SLE, IgA nephropathy
How do highly cationic Ags vs. highly anionic Ags vs. neutral Ags differ in where they deposit and form immune-complexes form in the glomerulus?
- Cationic (+) –> cross the GBM and form in subepithelial deposits
- Anionic (-) –> dont cross GBM and form subendothelially deposits
- Neutral charge –> tend to accumulate in the mesangium
Immune complexes deposited in which locations of the glomerulus are more likely to be involved in an inflammatory response due to be accessible to the circulation?
- Subendothelial portions of capillaries
- Mesangial locations
Immune complexes can form deposits:
- Subepithelial area (1)
- Epimembranous (2)
- Subendothelial area (3)
- Mesengial area (4)
Which nephropathies are most likely in each area?
1. Subepithelial humps (1)
- Acute glomerulonephritis
2. Epimembranous deposits (2)
- Membranous nephropathy
3. Subendothelial deposits (3)
- lupus nephritis
- membranoproliferative glomerulonephritis
- Mesenangial area (4)
* IgA nephropathy
Which coagulation factor may act as the stimulus for crescent formation associated w/ glomerular injury?
Thrombin
What is the most frequent clinical presentation of Focal Segmental Glomerulosclerosis?
- Nephrotic syndrome
- - Nonnephrotic proteinuria
Most common type of glomerular injury causing nephritic syndrome?
Immunologically mediated
What is the difference betwene primary and secondary glomerulonephritis?
- primary glomerulonephritis == disorders in which the kidney is the only/ predominant organ involved
-
secondary glomerulonephritis == when the glomerulus is affected by systemic immunologic diseases such as SLE, vascular disorders such as HTN, or m_etabolic diseases such as Fabry disease_
- glomerular diseases are often associated with systemic disorders (e.g. _diabetes mellitu_s, SLE, vasculitis, and amyloidosis)
________ are important for the maintenance of glomerular barrier function
visceral epithelial cells (i.e. podocytes);
separated from the endothelial cells by BM
- Diff types of glomerulopathies are characterized by one or more of four tissue changes.
- If acute vs chronic, what changes do we see?
- acute glomerular response to injury == hypercellularity and formation of crescents (if severe)
- chronic glomerular responses to injury ==BM thickening, hyalinosis, and sclerosis
